Uroporphyrinogen-Synthase in Erythrocyten bei akuter intermittierender Porphyrie: Neue pathobiochemische Aspekte

Abstract

Uroporphyrinogen synthase (EC 4.3.1.8) was determined in the erythrocytes of 380 patients, of which 21 showed clinical symptoms of acute intermittent porphyria. The normal range of a random sample was 61 +/- 23 mumol/1.h(x +/- 2s, n=302), including the activity of uroporphyrinogen cosynthase and the subsequent enzymes; when all the latter enzymes were destroyed by heating the haemolysate, the normal range for uroporphyrinogen synthase was 65 +/- 25 mumol/1.h(x +/- 2s, n=274). The respective activity of uroporphyrinogen synthase in patients with acute intermittent porphyria was 35 +/- 12, and 40 +/- 18 mumol/1.h which was significantly lower (p less than 0.001) than the control values. In the 21 cases of acute intermittent porphyria, the diagnosis had already been made from the presence of porphyrin precursors and porphyrin in the urine. In 7 of the 21 cases of acute intermittent porphyria, and in 6 relatives of the patients, the activity of the uroporphyrinogen synthase was in the overlap zone (40-50 mumol/1.h). 32 relatives of 9 of the patients with acute intermittent porphyria were investigated: 22 showed a significant decrease of uroporphyrinogen synthase, and 7 of these showed pathological urinary porphyrin precursors and porphyrin. The relative activity of uroporphyrinogen synthase in patients with acute intermittent porphyria was 57%. A decrease of the uroporphyrinogen synthase activity of greater than 30% compared with the mean of the controls is a sure indicator for the presence of a primary enzymic defect in the gene carrier for acute intermittent porphyria.